{"id":{"repo_id":"buffalo","oai_identifier":"oai:ubir.buffalo.edu:10477/79308"},"canonical_url":"https://search.dev.ndltd.org/etd/buffalo/oai:ubir.buffalo.edu:10477/79308","repository":{"repo_id":"buffalo","name":"Buffalo","base_url":"https://ubir.buffalo.edu/oai/request"},"display":{"title":"Quadruplex DNA Binders Based on Aromatic Tetraurea Macrocycles","abstract":"Ph.D.","abstract_html":"Ph.D.","abstract_has_math":false,"creators":["Detchou, Cadnel"],"institution":"State University of New York at Buffalo","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Gong, Bing","Chemistry"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2019,"date_issued":"2019-04-02T18:36:50Z","date_published":"2019-04-02T18:36:50Z","updated_at":"2026-07-27T19:05:14Z","subjects":["chemistry"],"languages":["eng"],"rights":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/10477/79308","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Gong, Bing","Chemistry"]},{"key":"dc:creator","label":"Author","values":["Detchou, Cadnel"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2019-04-02T18:36:50Z","2019","2018-12-22 01:16:15"]},{"key":"dc:publisher","label":"Institution","values":["State University of New York at Buffalo"]},{"key":"dc:type","label":"Dc Type","values":["Text","Dissertation"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["chemistry"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/10477/79308"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Ph.D.","G-quadruplexes are distinct secondary structures formed by DNA or RNA strands rich in guanine bases. These unique structures, often found in chromosomal extremities (telomeres) and intra-chromosomal region (oncogenes promoters), have been proven to play an important role in regulating oncogene expression and cell proliferation. Telomerase is a reverse transcriptase ribonucleoprotein found in rapidly proliferating cells but inactive in normal somatic cells and results in the lengthening of the telomeres. This lengthening has major consequences on the cell life cycle since it leads to immortalization. Efforts have been made to inhibit the activity of telomerase. The discovery of the natural product telomestatin, which was proven to bind and stabilize G-quadruplexes, result in indirect telomerase inhibition. The specific binding of G-quadruplexes by telomestatin has inspired the synthesis of small molecule analog that would mimic the potency of telomestatin toward telomerase through indirect inhibition. In this work, we have synthesized a series of aromatic tetraurea macrocycles which have been shown through Fluorescence Resonance Energy Transfer (FRET), Fluorescence Intercalation Displacement assays (G4-FID), Isothermal Titration Calorimetry (ITC), and Circular Dichroism (CD) to bind and induce the stabilization of human telomeric G-quadruplex 22AG (sequence (T2AG3)4). Chapter One presents an introduction on the polymorphism of G-quadruplex structures and an overview of the small molecules synthesized by other groups, along with the mode of interactions of these molecules with G-quadruplexes and methods used to study the binding of these ligands to G-quadruplex DNA. Chapter Two describes the synthesis, purification and characterization of our tetraurea macrocyclic molecules. Chapter Three presents results on the binding of our tetraurea macrocycles to G-quadruplex DNA by methods such as FRET, G4-FID, ITC and CD. Chapter Four gives the details of all experimental procedures including full 1HNMR, 13CNMR, MALDI or ESI MS spectra."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Quadruplex DNA Binders Based on Aromatic Tetraurea Macrocycles"]}]}],"canonical_facts":{"dc:contributor":["Gong, Bing","Chemistry"],"dc:creator":["Detchou, Cadnel"],"dc:date":["2019-04-02T18:36:50Z","2019","2018-12-22 01:16:15"],"dc:description":["Ph.D.","G-quadruplexes are distinct secondary structures formed by DNA or RNA strands rich in guanine bases. These unique structures, often found in chromosomal extremities (telomeres) and intra-chromosomal region (oncogenes promoters), have been proven to play an important role in regulating oncogene expression and cell proliferation. Telomerase is a reverse transcriptase ribonucleoprotein found in rapidly proliferating cells but inactive in normal somatic cells and results in the lengthening of the telomeres. This lengthening has major consequences on the cell life cycle since it leads to immortalization. Efforts have been made to inhibit the activity of telomerase. The discovery of the natural product telomestatin, which was proven to bind and stabilize G-quadruplexes, result in indirect telomerase inhibition. The specific binding of G-quadruplexes by telomestatin has inspired the synthesis of small molecule analog that would mimic the potency of telomestatin toward telomerase through indirect inhibition. In this work, we have synthesized a series of aromatic tetraurea macrocycles which have been shown through Fluorescence Resonance Energy Transfer (FRET), Fluorescence Intercalation Displacement assays (G4-FID), Isothermal Titration Calorimetry (ITC), and Circular Dichroism (CD) to bind and induce the stabilization of human telomeric G-quadruplex 22AG (sequence (T2AG3)4). Chapter One presents an introduction on the polymorphism of G-quadruplex structures and an overview of the small molecules synthesized by other groups, along with the mode of interactions of these molecules with G-quadruplexes and methods used to study the binding of these ligands to G-quadruplex DNA. Chapter Two describes the synthesis, purification and characterization of our tetraurea macrocyclic molecules. Chapter Three presents results on the binding of our tetraurea macrocycles to G-quadruplex DNA by methods such as FRET, G4-FID, ITC and CD. Chapter Four gives the details of all experimental procedures including full 1HNMR, 13CNMR, MALDI or ESI MS spectra."],"dc:format":["application/pdf"],"dc:identifier":["http://hdl.handle.net/10477/79308"],"dc:language":["eng"],"dc:publisher":["State University of New York at Buffalo"],"dc:rights":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."],"dc:subject":["chemistry"],"dc:title":["Quadruplex DNA Binders Based on Aromatic Tetraurea Macrocycles"],"dc:type":["Text","Dissertation"]},"updated_at":"2026-07-27T19:05:14Z"}